The antinociceptive effect of intracerebroventricularly administered prostaglandin D2 in the rat.

Intracerebroventricular administration of prostaglandin D2 (PGD2), the major PG in the rat brain, produced a dose-related anti-nociceptive effect in rats as assessed by the rat tail-hot wire, hot plate and phenylquinone-induced writhing techniques. The antinociceptive action of centrally-administered PGD2 was markedly attenuated after pretreatment of the rats with 5,6-dihydroxytryptamine, a selective neurotoxin for central serotonergic neurones, and p-chlorophenylalanine, a specific inhibitor of serotonin synthesis, indicating that the PGD2 action is serotonin-mediated. Naloxone, an antagonist of endogenous opioid receptors, also antagonised the antinociceptive action of PGD2. Earlier reports from this laboratory have shown that the antinociceptive action of centrally-administered PGE1 in rats is a serotonin-mediated effect and is also antagonised by naloxone. It was further shown that PGD2, like PGE1, augments serotonin turnover in the rat brain. The present findings support the view that PGD2 shares some of the central actions of PGEs and, like the latter, may function as a neuromodulator in the central nervous system.